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Expression of ADAM15 in lung carcinomas
1Institute of Pathology, University of Leipzig, Liebigstrasse 26, 04103, Leipzig, Germany. schuetza@medizin.uni-leipzig.de
Abstract:
ADAM15, a member of the ADAM (a disintegrin and metalloprotease) family, is a membrane protein containing both protease and adhesion domains and may, thus, be involved in tumor invasion and metastasis. The aim of this study was to analyze the expression of ADAM15 and its potential ligand, integrin alpha(v)beta3 (CD51/CD61), in lung carcinoma cell lines and tissues. Most small cell lung carcinomas (SCLCs) and non-SCLC cell lines were ADAM15, alpha(v) and beta3 integrin mRNA positive. Half of the cell lines expressed ADAM15, and three expressed the alpha(v)beta3 heterodimer at the cell surface as shown using flow cytometry. Paraffin sections of pulmonary epithelial tumors, including SCLCs (n=26), squamous cell cancer (SCCs, n=27) and adenocarcinomas (ACs, n=17) were stained with antibodies to the ectosolic and cytosolic domain of ADAM15 and alpha(v)beta3 integrin complex. The results were scored (0-12, according to Remmele's score). Normal epithelial cells of the lung were negative or slightly positive for ADAM15 (score<2). The score was always significantly higher for tumor cells. ACs showed the strongest staining (tumor center; ADAM15ecto; mean+/-SEM; 5.47+/-1.04), whereas SCLCs only showed weak ADAM15 expression (2.67+/-0.42; SCCs: 3.62+/-0.62). Frequently, significantly stronger ADAM15 expression has been shown in tumor cells located at the front of invasion compared with those within solid formations. Overall analysis of all tumor specimens and each tumor type revealed no significant correlation between tumor stage or degree of differentiation and ADAM15 ectosolic or cytosolic domain expression in tumor cells. Both molecules are often co-localized in the same tumor cells in ADAM15- and alpha(v)beta3 integrin-positive carcinomas. In summary, lung carcinoma cell lines and tissues were frequently ADAM15 positive.
Insights
ADAM15 expression is frequent in lung carcinoma cell lines and tissues, often co-localizing with integrin alpha(v)beta3. This suggests a role for ADAM15 in lung cancer progression and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- ADAM15, a metalloprotease, has domains suggesting involvement in tumor invasion and metastasis.
- Integrin alpha(v)beta3 is a potential ligand for ADAM15.
Purpose of the Study:
- To analyze ADAM15 and integrin alpha(v)beta3 expression in lung carcinoma cell lines and tissues.
- To investigate the correlation between ADAM15 expression and clinicopathological features.
Main Methods:
- Analysis of mRNA expression in lung carcinoma cell lines.
- Flow cytometry to detect cell surface expression of alpha(v)beta3 heterodimer.
- Immunohistochemical staining of tumor tissues for ADAM15 and alpha(v)beta3 integrin.
Main Results:
- Most small cell lung carcinoma (SCLC) and non-SCLC cell lines showed positive mRNA expression for ADAM15 and integrin subunits.
- Adenocarcinomas (ACs) exhibited the strongest ADAM15 staining, while SCLCs showed weak expression.
- ADAM15 expression was often higher in invasive tumor cells and frequently co-localized with alpha(v)beta3 integrin.
Conclusions:
- Lung carcinoma cell lines and tissues frequently express ADAM15.
- ADAM15 and integrin alpha(v)beta3 are often co-expressed in lung carcinomas.
- ADAM15 expression does not significantly correlate with tumor stage or differentiation.